6. Functions of the urinary system
Excretion
The removal of organic waste products from body fluids
Elimination
The discharge of waste products into the environment
Homeostatic regulation of blood plasma
Regulating blood volume and pressure
Regulating plasma ion concentrations
Stabilizing blood pH
Conserving nutrients

7. Tubular Functions Renal Clearance Studies
1. General: Powerful, relatively non-invasive, technique through which a great deal of renal function can be studied.

8. Figure 26.3 The Urinary System in Gross Dissection

9. Figure 26.4 The Structure of the Kidney
Figure 26.4a, b

10. Figure 26.5 The Blood Supply to the Kidneys
Figure 26.5a, b

11. Figure 26.6 A Representative Nephron

13. Nephron functions include:
Production of filtrate
Reabsorption of organic nutrients
Reabsorption of water and ions
Secretion of waste products into tubular fluid

14. Two types of nephron Cortical nephrons ~85% of all nephrons
Located in the cortex
Juxtamedullary nephrons
Closer to renal medulla
Loops of Henle extend deep into renal pyramids

15. Figure 26.7 Cortical and Juxtamedullary Nephrons
Figure 26.7a

16. Figure 26.7 Cortical and Juxtamedullary Nephrons
Figure 26.7b, c

17. Figure 26.9 An Overview of Urine Formation

18. Urine production maintains homeostasis
Regulating blood volume and composition
Excreting waste products
Urea
Creatinine
Uric acid

19. Basic processes of urine formation
Filtration
Blood pressure
Water and solutes across glomerular capillaries
Reabsorption
The removal of water and solutes from the filtrate
Secretion
Transport of solutes from the peritubular fluid into the tubular fluid

20. Functional anatomy of the nephron
Proximal convoluted tubule (PCT)
Actively reabsorbs nutrients, plasma proteins and ions from filtrate
Released into peritubular fluid
Loop of Henle
Descending limb
Ascending limb
Each limb has a thick and thin section

21. Functional anatomy of the nephron
Distal convoluted tubule (DCT)
Actively secretes ions, toxins, drugs
Reabsorbs sodium ions from tubular fluid

23. Figure 26.8 The Renal Corpuscle
Figure 26.8a, b

24. Figure 26.8 The Renal Corpuscle
Figure 26.8c, d

25. Figure 26.10 Glomerular Filtration
Figure 26.10a, b

26. Glomerular filtration rate (GFR)
Amount of filtrate produced in the kidneys each minute
Factors that alter filtration pressure change GFR

27. Figure 26.11 The Response to a Reduction in the GFR
Figure 26.11a

28. Reabsorption and secretion at the PCT
Glomerular filtration produces fluid similar to plasma without proteins
The PCT reabsorbs 60-70% of the filtrate produced
Reabsorption of most organic nutrients
Active and passive reabsorption of sodium and other ions
Reabsorption of water
Secretion also occurs in the PCT

29. Figure 26.12 Transport Activities at the PCT

30. CA = carbonic anhydrase
THE TRANSPORTERS
Glomerular Filtrate (plasma-like)
Proximal Tubule Reabsorbs:
high in Na+, Cl-, HCO3-, glucose, etc.
Na+, Cl-, HCO3-, H2O, glucose, amino acids, and more
Cl-
Cl- 3 4
Na/H
HCO H+
H+ + HCO3-
CO2 + H2O CA
Na+
HCO3-
CO2 + H2O 5 CA
R. 380
CA = carbonic anhydrase

31. Review of Renal Tubular mechanisms for H+ secretion & excretion
Reabsorption of filtered HCO3-: predominantly in proximal tubule
conservation
reabsorption of filtered HCO3
+ H2O
CA (brush border) CA

32. H+ H+ secretion H+ excretion ATP ATP new HCO3- absorbed in urine
Some Transporters
Apical Na+/H+ exchanger
Apical H+-ATPase (ATP-dep. pump)
Apical H+/K+-ATPase (pump)
Apical Na+/NH4+ exchanger
Basolateral Na+-HCO3- co-transporter
HPO42-
Cl- Ex Co
HCO3-
H+ secretion
Cl-
Na+ H+ Ex
HCl
HPO42- K+ H+
ATP H+ Co H+
H2PO4-
ATP
new HCO3- absorbed
H+ excretion Ex Co
in urine

33. acidosis
alkalosis

34. Respiratory and Renal Compensatory Mechanisms for ACID-BASE Disturbance

35. Summary of Principal Proximal Tubular Transport Mechanisms
Na+-coupled co-transporters
Na+-H+ exchanger
Apical membrane
Basolateral membrane
also there are water channels (Aquaporins) in the apical and basolateral membranes
Na+ 3 1
(other stoichiometry possible, e.g., 2:1)

36. The loop of Henle and countercurrent multiplication
Between ascending and descending limbs of loop
Creates osmotic gradient in medulla
Facilitates reabsorption of water and solutes before the DCT
Permits passive reabsorption of water from tubular fluid

39. Function of the vasa recta
Removes solutes and water
Balances solute reabsorption and osmosis in the medulla

40. Figure 26.13 Countercurrent Multiplication and Concentration of Urine
Figure 26.13b

41. Figure 26.13 Countercurrent Multiplication and Concentration of Urine

42. Figure 26.13 Countercurrent Multiplication and Concentration of Urine
Figure 26.13a

43. Reabsorption and secretion at the DCT
DCT performs final adjustment of urine
Active secretion or absorption
Absorption
Tubular cells actively resorb Na+ and Cl-
In exchange for potassium or hydrogen ions (secreted)

44. Figure 26.14 Tubular Secretion and Solute Reabsorption at the DCT

45. Figure 26.14 Tubular Secretion and Solute Reabsorption at the DCT
Figure 26.14c

46. Reabsorption and secretion along the collecting system
Water and solute loss is regulated by aldosterone and ADH
Reabsorption
Sodium ion, bicarbonate, and urea are resorbed
Secretion
pH is controlled by secretion of hydrogen or bicarbonate ions

48. Figure 26.16 A Summary of Renal Function

49. Figure 26.11 The Response to a Reduction in the GFR
Figure 26.11b

50. Sympathetic activation
Produces powerful vasoconstriction of afferent arterioles
Decreases GFR and slows production of filtrate
Changes the regional pattern of blood flow
Alters GFR
Stimulates release of renin by JGA

51. Hypothalamus, posterior pituitary and ADH secretion– connection with baroreceptors

53. Synthesis of ADH
It is synthesized as pre-prohormone and processed into a nonapeptide (nine amino acids).
Six of the amino acids form a ring structure, joined by disulfide bonds.
It is very similar in structure to oxytocin, differing only in amino acid #3 and #8.
ADH synthesized in the cell bodies of hypothalamic neurons in the supraoptic nucleus
ADH is stored in the neurohypophysis (posterior pituitary)—forms the most readily released ADH pool

54. Hypothalamus and posterior pituitary

55. Structure of ADH

56. Synthesis of ADH
Mechanical disruption or the neurohypohyseal tract by trauma, tumor, or surgery temporarily causes ADH deficiency.
ADH will be restored after regeneration of the axons (about 2 weeks).
But if disruption happens at a high enough level, the cell bodies die in the hypothalamus resulting in permanent ADH deficiency

57. Primary action of ADH: antidiuresis
ADH binds to V2 receptors on the peritubular (serosal) surface of cells of the distal convoluted tubules and medullary collecting ducts.
Via adenylate cyclase/cAMP induces production and insertion of AQUAPORIN into the luminal membrane and enhances permeability of cell to water.
Increased membrane permeability to water permits back diffusion of solute-free water, resulting in increased urine osmolality (concentrates urine).

58. ADH increases renal tubular absorption of water

59. Figure 26.15 The Effects of ADH on the DCT and Collecting Ducts
Figure 26.15a, b

63. ADH and blood pressure

64. ADH and plasma osmolality

65. Pathway by which ADH secretion is lowered and water excretion raised when excess water is ingested

66. Pathway by which ADH secretion and tubular permeability to water is increased when plasma volume decreases

67. Aldosterone synthesis
Aldosterone is synthesized and secreted by the zona glomerulosa .
The synthesis of aldosterone from cholesterol to corticosterone is identical to the synthesis of glucocorticoids in the zona fasiculata.
The C18 methyl group of corticosterone is hydroxylated and converted to an aldehyde yielding aldosterone.

68. Aldosterone synthesis in the adrenal zona glomerulosa

69. Aldosterone function
The principal function of aldosterone is to sustain extracellular fluid volume by conserving body sodium.
Aldosterone is largely secreted in response to signals that arise from the kidney when a reduction in circulating fluid volume is sensed.
When body sodium is depleted, the fall in extracellular fluid and plasma volume decreases renal arterial blood flow and pressure.

70. The kidney is the major site of mineralocorticoid activity.
Aldosterone action
Aldosterone binds to the mineralocorticoid receptor in target cells and affects transcriptional changes typical of steroid hormone action.
The kidney is the major site of mineralocorticoid activity.

71. Increased blood pressure results from excess aldosterone.
Aldosterone action
Increased blood pressure results from excess aldosterone.
Hypertension is an indirect consequence of sodium retention and expansion of extracellular fluid volume.

72. Aldosterone action
Aldosterone stimulates the active secretion of potassium from the tubular cell into the urine.
Most potassium that is excreted daily results from distal tubular secretion.
Hence aldosterone is critical for disposal of daily dietary potassium load at normal plasma potassium concentrations.

73. Regulation of aldosterone secretion: Activation of renin-angiotensin system in response to hypovolemia is predominant stimulus for aldosterone synthesis.

74. Pathway by which aldosterone secretion and tubular sodium reabsorption is increased when plasma volume is decreased

75. Pathway by which an increased potassium intake induces greater potassium excretion mediated by aldosterone

76. Aldosterone
Angiotensin II acts on the zona glomerulosa to stimulate aldosterone synthesis.
Angiotensin II acts via increased intracellular cAMP to stimulate aldosterone synthesis.

77. Aldosterone mechanism
The aldosterone-induced proteins serum and glucocorticoid-inducible kinase (Sgk), corticosteroid hormone-induced factor (CHIF), and Kirsten Ras (Ki-Ras) increase the activity and/or no. of these transport proteins during the early phase of action

78. Aldosterone Action

79. Aldosterone time course of action

80. Action of aldosterone on the renal tubule
Action of aldosterone on the renal tubule. Sodium reabsorption from tubular urine into the tubular cells is stimulated. At the same time, potassium secretion from the tubular cell into urine is increased. Na+/K+-ATPase, and Na+ channels work together to increase volume and pressure, and decrease K+.

81. Horacio J. Andorgué & Nicolaos E. Midias

82. Cortisol is at 1000 fold higher concentrations than aldosterone